Mucosal IgA immune complex induces immunomodulatory responses in allergic airway and intestinal Th2 disease.

BACKGROUND: IgA is the most abundant Immunoglobulin at the mucosal surface and its role in regulating mucosal immunity is not fully understood, but its presence is associated with protection from developing allergic disease.

OBJECTIVE: Determine the role of IgA immune complexes for therapeutic application to mucosal allergic responses.

METHODS: Apply TNP specific IgA immune complexes, using TNP coupled Ovalbumin, to airway and gut mucosal surfaces in systemically sensitized allergic animals to regulate allergen challenge responses. Animals were assessed for both pathologic and immune mediated responses in lung or gut, respectively, using established mouse models.

RESULTS: The mucosal application of IgA immune complexes in the lung and gut with TNP/ovalbumin regulated Th2 driven allergic response in the lung and gut, reducing Th2 cytokines and mucus (lung) as well as diarrhea and temperature loss (gut), while increasing IL-10 and Treg cells. The IgA-ovalbumin immune complex did not alter peanut induced anaphylaxis indicating antigen specificity. Using ovalbumin specific DO.11-GFP IL-4 reporter mouse derived Th2 skewed cells in a transfer model demonstrated that mucosal IgA immune complex treatment reduced Th2 cell expansion and increased Treg cell numbers. To address a potential mechanism of action, TGFβ and IL-10 were induced in bone marrow-derived DC when they were exposed to IgA immune complex, suggesting a regulatory phenotype induced in DC that also led to an altered primary T cell mediated response in in vitro ovalbumin specific assays.

CONCLUSION: These studies highlight one possible mechanism of how allergen-specific IgA may provide a regulatory signal to reduce the development of allergic responses in lung and gut.